AUTHOR=Yu Zhijian , Zhang Zhengrong , Shi Lile , Hua Shengni , Luan Ting , Lin Qiuping , Zheng Zhixiong , Feng Xiaosan , Liu Mubiao , Li Xiaobin 

TITLE=In silico characterization of IncX3 plasmids carrying blaOXA-181 in Enterobacterales

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.988236

DOI=10.3389/fcimb.2022.988236

ISSN=2235-2988

ABSTRACT=<p>Carbapenem-resistant <italic>Enterobacterales</italic> poses a global urgent antibiotic resistance threat because of its ability to transfer carbapenemase genes to other bacteria <italic>via</italic> horizontal gene transfer mediated by mobile genetic elements such as plasmids. Oxacillinase-181 (OXA-181) is one of the most common OXA-48-like carbapenemases, and OXA-181-producing <italic>Enterobacterales</italic> has been reported in many countries worldwide. However, systematic research concerning the overall picture of plasmids harboring <italic>bla</italic><sub>OXA-181</sub> in <italic>Enterobacterales</italic> is currently scarce. In this study, we aimed to determine the phylogeny and evolution of <italic>bla</italic><sub>OXA-181</sub>-positive (gene encoding OXA-181) plasmids. To characterize the plasmids harboring <italic>bla</italic><sub>OXA-181</sub> in <italic>Enterobacterales</italic>, we identified 81 <italic>bla</italic><sub>OXA-181</sub>-positive plasmids from 35,150 bacterial plasmids downloaded from the NCBI RefSeq database. Our results indicated that diverse plasmid types harbored <italic>bla</italic><sub>OXA-181</sub> but was predominantly carried by IncX3-type plasmids. We systematically compared the host strains, plasmid types, conjugative transfer regions, and genetic contexts of <italic>bla</italic><sub>OXA-181</sub> among the 66 <italic>bla</italic><sub>OXA-181</sub>-positive IncX3 plasmids. We found that IncX3 plasmids harboring <italic>bla</italic><sub>OXA-181</sub> were mostly ColKP3-IncX3 hybrid plasmids with a length of 51 kb each and were mainly distributed in <italic>Escherichia coli</italic> and <italic>Klebsiella pneumoniae</italic>. Most of the IncX3 plasmids harboring <italic>bla</italic><sub>OXA-181</sub> were human origin. Almost all the <italic>bla</italic><sub>OXA-181</sub>-positive IncX3 plasmids were found to carry genes coding for relaxases of the MOB<sub>P</sub> family and VirB-like type IV secretion system (T4SS) gene clusters, and all the 66 IncX3 plasmids were found to carry the genes encoding type IV coupling proteins (T4CPs) of the VirD4/TraG subfamily. Most IncX3 plasmids harbored both <italic>bla</italic><sub>OXA-181</sub> and <italic>qnrS1</italic> in their genomes, and the two antibiotic resistance genes were found to a composite transposon bracketed by two copies of insertion sequence IS<italic>26</italic> in the same orientation. Our findings provide important insights into the phylogeny and evolution of <italic>bla</italic><sub>OXA-181</sub>-positive IncX3 plasmids and further address their role in acquiring and spreading <italic>bla</italic><sub>OXA-181</sub> genes in <italic>Enterobacterales</italic>.</p>